crossing96/oncoscreening huggingface dataset:
Totally intracorporeal 3D laparoscopic orthotopic neobladder reconstruction following radical cystectomy for infiltrative bladder tumors: the experience of modified Studer and modified Y-shaped ileal reconstruction techniques.	PURPOSE: We report our experience with 23 cases in utilizing ileum to perform totally intracorporeal 3D laparoscopic neobladder reconstruction using two different surgical techniques. METHODS: Patients candidates for reconstructive surgery were in a good biological status with a body mass index (BMI) in the range of 18.5-25 and presented a muscle-infiltrative bladder tumor with negative nodal frozen sections performed during the operation. Twenty-one modified Studer neobladder and 2 modified Y-shaped neobladder techniques for totally intracorporeal 3D laparoscopic ileal neobladder cases were performed using drawings and intra-operative images. An emphasis was made on different tips and tricks that can be applied when using ileum for the neobladder reconstruction, to avoid surgical complications and obtain optimal functional results. RESULTS: The operations were performed in a mean time of 5 h, with a mean blood loss of 350 ml and grade II postoperative Clavien Dindo complications. The 23 patients were discharged after a mean hospital stay of 21 days and had a functional ileal neobladder after a mean of 30 days. The results were monitored also on the long-term, taking into account functional results and possible complications from utilizing ileum as a urinary reservoir. CONCLUSION: Resecting a digestive segment and using it as a urinary reservoir may lead to multiple complications. Therefore, laparoscopic technical adaptations and highly skilled surgical teams are required for performing a totally intracorporeal 3D laparoscopic orthotopic ileal neobladder reconstruction.	bladder
Heptaphylline suppresses the proliferation and migration of human bladder cancer cells via induction of intrinsic apoptosis, autophagy and inhibition of β-catenin signalling pathway.	PURPOSE: Heptaphylline has been shown to suppress the growth of different types of cancer cells. Nonetheless, the anticancer effects of Heptaphylline have not been examined against human bladder cancer cells. Against this backdrop, this study was undertaken to investigate the anticancer effects of the carbazole alkaloid Heptaphylline against human bladder cancer cells. METHODS: Proliferation rate was determined by MTT assay. Apoptosis was demonstrated by DAPI and annexin V/propidium iodide (PI) assay. Electron microscopy was used for autophagy detection. Western blot analysis was used to determine protein expression. RESULTS: The results showed that Heptaphylline suppressed the proliferation of the RT4 bladder cancer cells and exhibited an IC50 of 25 µM. The toxic effects of Heptaphylline were comparatively lower on the normal Hs172.T cells, as evidenced from the IC50 of 95 µM. The wound healing assay showed that Heptaphylline suppressed the migration of the RT4 bladder cancer cells. The DAPI and annexin V/PI staining showed that Heptaphylline induced apoptosis in the RT4 bladder cancer cells which was also accompanied by enhancement in the cleavage of PARP, caspase-3 and caspase-9. Additionally, Heptaphylline caused increase in Bax and decrease in Bcl-2 expression. Electron microscopic analysis showed that Heptaphylline also caused autophagy in the RT4 cells which was associated with increase in LC3, Atg5, Atg7 and Beclin-1 expression and decrease in p62 expression. This molecule also blocked the β-catenin signalling pathway in the RT4 bladder cancer cells. CONCLUSION: Taken together, Heptaphylline suppressed the proliferation of the bladder cancer cells and may prove beneficial in the bladder cancer treatment.	bladder
A microfluidic system based on the monoclonal antibody BCMab1 specifically captures circulating tumor cells from bladder cancer patients.	Circulating bladder tumor cells provide significant information for cancer diagnosis, tumor staging and personalized cancer therapy. Previous studies have reported various methods for capturing circulating tumor cells; however, capturing circulating tumor cells remain a challenge. Here, we present a microfluidic chip with high specificity and capture yields that we refer to as a bladder cancer diagnosis chip. We show that this chip can be used to effectively capture circulating bladder cancer cells based on antibody-BCMab1, a monoclonal antibody that binds to aberrantly glycosylated integrin a3b1. This capture platform is composed of a polydimethylsiloxane (PDMS) chip, whose microchannels are functionalized with biotinylated BCMab1. To change the direction of flow to increase cell-substrate contact, we also introduced a herringbone or chevron channel pattern into the chip. Using this system, we were able to capture bladder cancer cells with high specificity. The capture rates of the bladder cancer diagnosis chip were evaluated at different flow rates and cell concentrations. We found that 90% of the cancer cells were successfully captured at flow rates of 10 μL/min and at various cell concentrations. This highly specific microfluidic chip is a novel tool for bladder cancer diagnosis and offers an opportunity for personalized treatment.	bladder
Evaluation of ASPM and TEF Gene Expressions as Potential Biomarkers for Bladder Cancer.	Bladder cancer is one of the most predominant tumors of the genitourinary tract. In addition to pathological findings, the molecular modifications that might affect tumorigenesis and tumor outcome should be considered when treating bladder cancer. Accordingly, we aimed to investigate the expression levels of both the ASPM and TEF genes in bladder cancer tissues and their value in disease prognosis. The expression levels of the ASPM and TEF genes were analyzed by quantitative real-time PCR (qRT-PCR) in 90 bladder cancer tissue specimens and 90 specimens of normal urinary bladder tissue taken away from the tumor site. The upregulation of ASPM expression and the downregulation of TEF expression were observed in bladder cancer tissues compared to adjacent normal tissues, and these levels were correlated with high-grade tumors, advanced stage disease and the presence of metastasis. Both genes had the ability to predict metastatic association with sensitivity (84.62%) and specificity (68.42%; *P < 0.001) for the ASPM gene and for the TEF gene with sensitivity (80.77%) and specificity (78.95%; *P < 0.001). Additionally, Kaplan-Meier survival analysis indicated that elevated ASPM expression levels and reduced TEF expression levels significantly correlated with decreased overall survival and progression-free survival. The current analysis concludes that ASPM and TEF expressions might be used as potential biomarkers in bladder cancer patients.	bladder
Neoadjuvant Gemcitabine-Cisplatin Plus Radical Cystectomy-Pelvic Lymph Node Dissection for Muscle-invasive Bladder Cancer: A 12-year Experience.	INTRODUCTION: The aim of this study was to determine drug delivery/toxicity, and pathologic/surgical outcomes of patients with muscle-invasive bladder cancer (MIBC) receiving neoadjuvant gemcitabine-cisplatin (GC) plus radical cystectomy-pelvic lymph node dissection (RC-PLND). PATIENTS AND METHODS: Chemotherapy and surgical/pathologic outcomes were retrospectively analyzed with 5-year survival follow-up at a referral center. Post-neoadjuvant chemotherapy (NAC) pathologic endpoints included complete response (pT0N0), residual non-MIBC (pTa/Tis/T1N0), and ≥ MIBC (≥ pT2 and/or N+). Associations of pathologic/surgical findings with overall survival (OS), disease-free survival (DFS), and surgical management with RC-PLND were analyzed (Cox regression). RESULTS: Clinical T2a-T4aN0M0 MIBC patients (n = 154) from January 2000-October 2012 received GC plus RC-PLND. Patients (n = 117; 76%) received GC × 4 and 136 (88%) GC × 3. Five-year OS was 61% (95% confidence interval [CI], 53-71). Median number of resected lymph nodes (LNs) was 19. Down-staging was observed as follows: pT0N0: 21%; pTa/Tis/T1N0: 25%, with similar 5-year OS (85% and 89%, respectively). Five-year OS for < pT2 versus ≥ pT2 residual disease was 87% (95% CI, 78%-98%) versus 38% (95% CI, 27%-53%); P < .001. Post-NAC stage ≥ pT2 (HR, 6.79; 95% CI, 2.63-17.53; P < .001), positive LN (HR, 3.64; 95% CI, 1.84-7.19; P < .001), and positive margins (HR, 4.15; 95% CI, 1.68-10.25; P = .002) were associated with increased risk of all-cause death (multivariable analysis). An HR of 0.97 (95% CI, 0.94-1.00) was observed for each additional node removed, but this effect was not statistically significant (P = .056). CONCLUSIONS: Neoadjuvant GC achieves meaningful pathologic responses. Patients with ≥ pT2 residual disease, positive margins, or positive LN post-chemotherapy have inferior survival.	bladder
HOXA10 promotes the development of bladder cancer through regulating FOSL1.	OBJECTIVE: This study was aimed to investigate the expression characteristics of HOXA10 in bladder cancer (BCa), and to further study whether it can promote the development of BCa via regulating FOSL1. PATIENTS AND METHODS: The expression of HOXA10 was examined by quantitative Real Time-PCR (qRT-PCR) in 37 pairs of tumor tissue and paracancerous specimens of BCa patients; meanwhile, in BCa cell lines, the expression of HOXA10 was also verified using qRT-PCR. Subsequently, after HOXA10 knockdown model was constructed in BCa cell lines (EJ and J82) using lentivirus transfection, transwell, as well as wound healing assays, were performed to analyze the influence of the downregulation of HOXA10 on the biological function of BCa cells. Finally, Luciferase reporting assay and cell reverse experiment were applied to explore the specific interaction between HOXA10 and FOSL1. RESULTS: The results of qRT-PCR indicated that the expression level of HOXA10 in BCa tissue samples was remarkably higher than that in adjacent normal ones, with a statistically significant difference. At the same time, the overall survival rate of patients with high expression of HOXA10 was found to be lower than those with low expression. Meanwhile, compared with cells in sh-NC group, the metastasis ability of BCa cells in sh-HOXA10 group was remarkably weakened. In addition, it was found that the levels of FOSL1 and HOXA10 were negatively correlated in BCa tissues. The result of the Luciferase reporter gene assay revealed that HOXA10 could be targeted by FOSL1 through certain binding sites between them. In addition, HOXA10 was found to be capable of further regulating the malignant progression of BCa by modulating FOSL1. CONCLUSIONS: HOXA10 expression is remarkably elevated in BCa tissues and cell lines, which is closely relevant to the poor prognosis of BCa patients. In addition, HOXA10 may be able to accelerate BCa metastasis via modulating FOSL1 expression.	bladder
Combining two grading systems: the clinical validity and inter-observer variability of the 1973 and 2004 WHO bladder cancer classification systems assessed in a UK cohort with 15 years of prospective follow-up.	PURPOSE: Paucity of reliable long-term data on the prognostic implications of the 2004 WHO bladder cancer classification system necessitates utilisation of both this and the 1973 grading systems. This study evaluated, in noninvasive (pTa) bladder tumours, the prognostic value of the 2004 system independently and in combination with the 1973 system while establishing concordance between tertiary centre uropathologists. METHODS: We used a cohort of non-muscle invasive bladder cancer (NMIBC) patients diagnosed between 1991 and 93 where tumour features were gathered prospectively with detailed cystoscopic follow-up data recorded over 15 years. Initial grading was by one senior expert uropathologist (UP1) using the 1973 WHO classification alone. Subsequently, two other expert uropathologists (UP2 and UP3), blinded to the previous grading, re-evaluated the pathology slides and graded the tumours using both the 1973 and 2004 systems. Association between grade and recurrence/progression was analysed and the Cohen Kappa test assessed concordance between pathologists. RESULTS: Of 370 new NMIBC, 229 were staged noninvasive (pTa). Recurrence rates were 46.2% and 50.0% for LGPUC (low-grade papillary urothelial carcinoma) and HGPUC (high-grade papillary urothelial carcinoma), respectively, while progression was seen in 3.9% and 10.0% of LGPUC and HGPUC, respectively. Concordance between uropathologists UP2 and UP3 for the 2004 and 1973 systems was good (Kappa = 0.69) and fair (Kappa = 0.25), respectively. CONCLUSIONS: With good inter-observer concordance, the 2004 WHO classification system of noninvasive bladder tumours appears to accurately predict recurrence and progression risks. The combination of both grading systems to low-grade tumours allows further refinement of the natural history.	bladder
ROC-1, P21 and CAIX as markers of tumor aggressiveness in bladder carcinoma in Egyptian patients.	BACKGROUND: Bladder cancer (BC) is one of the most common malignancies in Egypt, representing about 8.7% of cancers in both sexes with more predominance in males, making identification of valuable predictive and prognostic markers, mandatory. Cullin-RING ligases (CRL) play an important role in the ubiquitination of cell cycle-related proteins or other proteins (e.g., DNA replication protein, signal transduction protein). Regulator of Cullins-1 (ROC-1) is a key subunit of CRL. P21 belongs to the family of cyclin dependent kinase inhibitors (CKIs) which regulates cell cycle by inactivating Cyclin- Dependent Kinases key regulators of the cell cycle. CAIX a highly active member of the family of carbonic anhydrases has gained much interest as a hypoxic marker. Hypoxia is a consequence of the rapid growth of many tumors, including bladder cancer, and is an important regulator of gene expression and resistance to chemotherapy and radiotherapy. Therefore the purpose of this study is to evaluate the role of ROC-1, CAIX and P21 and its relationship with the clinico-pathological features of bladder cancer in Egyptian patients. METHODS: Using the standard immunohistochemical technique, ROC-1, CAIX and P21 expression in 80 primary bladder carcinomas and 15 normal bladder specimens as control group were assessed. The bladder carcinoma cases included 50 cases with muscle invasive bladder cancer and 30 cases with non-muscle invasive bladder cancer. RESULTS: Over expression of ROC-1, CAIX and P21 in BC were significantly associated with muscularis propria invasion and high grade BC. ROC-1, CAIX and P21, showed significant inverse relationship in primary BC cases. CAIX expression was significantly higher in BC compared with controls. Regarding the survival analysis, expression of ROC-1, CAIX and P21 didn't affect the survival of BC patients. CONCLUSIONS: High expression of ROC-1, CAIX and P21 could be promising potential biomarkers for identifying patients with poor prognostic factors in bladder cancer serving as potential targets for cancer therapy.	bladder
Late Recurrences Following Radical Cystectomy Have Distinct Prognostic and Management Considerations.	PURPOSE: Disease recurrence after radical cystectomy generally occurs within 2 years and has a poor prognosis. Less well defined are the outcomes in patients who experience a late recurrence (more than 3 years after radical cystectomy). We report our institutional experience with late recurrences and describe the relationships between time to recurrence, management strategies and survival. MATERIALS AND METHODS: The study cohort comprised 2,315 patients who underwent radical cystectomy for urothelial carcinoma at our center between 2000 and 2014, of whom 617 had a recurrence. Median followup for survivors was 2.6 years after recurrence (IQR 0.95-4.5). For the study we considered disease recurrence as recurrences outside the urinary tract. We compared baseline characteristics and post-recurrence management between those with recurrence 3 or less and more than 3 years after radical cystectomy. RESULTS: A total of 58 patients with late recurrence had significantly lower consensus T stage and lower frequency of nodal involvement. The average 1-year bladder cancer death rate from the time of recurrence declined from 66% to 50% to 33% for patients with recurrence times of 6 months, 2 years, and 5 years after radical cystectomy, respectively. For patients who survived at least 1 year after recurrence, the estimated survival at 5 years after recurrence was 45% for those with late recurrence and 21% for patients who had an early recurrence. Local consolidative therapy (metastasectomy or radiation) was more common in patients with late recurrence (19% vs 3.6%, p <0.0001). Cancer specific survival in early recurring cases was significantly worse than in late recurring cases in the subset receiving local consolidation (p=0.02). CONCLUSIONS: The prolonged lifespan of patients experiencing a late recurrence after radical cystectomy can be leveraged to individualize management. There is strong rationale for investigating the role of metastasectomy in the management of late recurrences.	bladder
Genetic and molecular biology of bladder cancer among Iranian patients.	BACKGROUND: Bladder cancer (BC) is the sixth common cancer among Iranians. Various risk factors such as smoking, body mass index, chronic infection, age, and genetic factors are associated with BC progression. METHODS: It has been shown that a significant ratio of patients have tumors with muscle bladder layer invasion and poor prognosis at the time of diagnosis. Therefore, the early detection of tumors is required to reduce the mortality rate of BC cases. Since there is a wide geographical incidence variation in BC in Iran, it seems that the ethnic and genetic factors can be the main risk factors among Iranian BC patients. RESULTS: For the first time, in present review we have summarized all of the reported genes among Iranian BC patients until now which were significantly associated with tumorigenesis. Moreover, we categorized all of the reported genes based on their cell and molecular functions to clarify the genetic and molecular biology of BC among Iranian population. CONCLUSION: This review paves the way of determination of a population-based genetic panel markers for the early detection of BC in this population.	bladder
Prospective evaluation of a urinary biomarker panel to detect and predict recurrence of non-muscle-invasive bladder cancer.	PURPOSE: To perform a feasibility phase study of a panel of putative protein biomarkers and determine whether it can identify and predict tumor recurrence in patients with non-muscle-invasive bladder cancer (NMIBC) on follow-up. METHODS: We prospectively analyzed the urine of 152 patients previously treated for NMIBC. Quantitative expression of plasminogen activator inhibitor-1 (PAI-1), DJ-1, apolipoprotein A-I (apoA-1), matrix metallopeptidase-9 (MMP-9), and interleukin-8 (IL-8) was assessed by enzyme-linked immunosorbent assay and compared amongst patients with and without bladder cancer recurrence at urine collection and during 3 years of follow-up. Tumor recurrence was confirmed by pathologic analysis. We performed a prediction analysis, excluding patients with recurrence at the start of the study, and assessed the influence of previous use of intravesical BCG on the level of biomarkers. RESULTS: Median follow-up time was 47 months (interquartile range 39-50 months). Sixteen patients (10.5%) were diagnosed with recurrence at the start of the study, and 21 (15.4%) were diagnosed during the study. Three biomarker proteins (apoA-1, MMP-9, and IL-8) appear to hold diagnostic potential [odds ratio (OR) = 12.9; 95% CI 3.5-47.4]; while, PAI-1 and IL-8 predict recurrence (OR = 4.1; 95% CI 1.4-11.4). Previous use of intravesical BCG did not affect biomarker levels. CONCLUSION: In the feasibility phase, the panel of urine biomarkers analyzed detected and predicted recurrence of NMIBC and provided reliable results in patients who had previously used intravesical BCG. Validation studies are required to confirm the panel clinical utility.	bladder
Urinary Exosomes from Bladder Cancer Patients Show a Residual Cancer Phenotype despite Complete Pathological Downstaging.	Invasive urinary bladder cancer shows high recurrence rates after cystectomy even with apparent complete downstaging at cystectomy. Exosomes are nano-sized vesicles important in cell-cell communication, which have been hypothesized to contribute to cancer dissemination and recurrence. The aim of this study was to investigate if pro-carcinogenic exosomes could be detected in urine from histologically downstaged bladder cancer patients. 13 Patients were included in this study. Paired ureter and urine samples from nine patients underwent mass spectrometry, while samples from the remaining patients were used for exosome characterization. At cystectomy, exosomes were isolated from bladder and ureter urine, whereafter quantitative proteome profiling was performed. Urinary exosomes clustered based on whether they came from the bladder, with tumour contact, or the ureters, without tumour contact, even though all came from completely downstaged patients. Proteins overexpressed in exosomes derived from bladder urine contained several oncogenes and were mainly associated with tumour metabolism pathways. Although patients were histologically tumour-free at cystectomy, the bladder urine contained exosomes with a carcinogenic metabolic profile. This suggests a continuous release of exosomes from the bladder, which may promote recurrence at distant sites through metabolic rewiring, even after apparent complete downstaging. These exosomes, coming from either undetected cancer cells or partly transformed cells, are likely to increase the risk of metastasis and encourages cystectomy even in completely downstaged patients.	bladder
Bladder Cancer and Google Trends: Associations Between US Search Patterns and Disease Outcomes May Show Need for Improved Awareness Strategies.	"Interest in and awareness of bladder cancer may translate to better health-seeking behaviors and earlier detection, given modifiable risk factors such as smoking. We assessed bladder cancer interest in the USA over the past 15 years as reflected by Internet search trends, and correlated these trends with epidemiologic patterns in bladder cancer. Google Trends was used to estimate US bladder cancer interest in the unit search volume index (SVI), which estimates the volume of online search activity for a specified period relative to the highest volume of searches within a specified location. Between January 2004 and June 2019, SVIs were collected for the search term ""bladder cancer"" and other related search terms. To evaluate the effect of public awareness campaigns, the SVIs for the month of May (US bladder cancer awareness month) were compared with the SVIs of all other months. Correlations between ""bladder cancer"" SVI and incidence, mortality, and mortality-to-incidence ratio (proxy for survival) by state were evaluated. There was no increase in the relative search volumes for ""bladder cancer"" during the national bladder cancer awareness month compared with all other months (p = 0.27). By state, there were positive correlations between SVIs of ""bladder cancer"" and incidence (R = 0.72, p < 0.001) and mortality (R = 0.47, p < 0.001). However, there was no correlation between SVIs and mortality-to-incidence ratio (R = - 0.24, p = 0.08). Interest in bladder cancer is positively associated with disease incidence and mortality but not survival, suggesting interest is driven by new diagnoses or deaths, and not early detection that can improve survival. Our findings may show the need for better public education endeavors."	bladder